Recent developments in biological imaging have pushed the limits of existing microscopes. The instabilities inherent in microscopes lead to positional drift of the imaged sample, and this compromises the precision and accuracy of the imaging. A major contributor to microscope instabilities is sample drift (Carter et al., 2007). Sample drift, or positional drift, is simply movement of the sample relative to the imaging sensor (such as a camera), and it can occur in all three dimensions. For conventional fluorescence microscopy, where resolutions on the order of 500 nm are obtained, sample drifts of 200 nm may be tolerable. In localization-based microscopy a drift of 200 nm or more during acquisition may destroy the high resolution nature of the image. Furthermore, long data acquisition times inherent in localization-based imaging place even higher demands on the stability of the microscope. These methods may routinely take hours to obtain a single image. In localization-based Super Resolution methods, maintenance of microscope stability for very long periods of time is desirable. Approaches that attempt to correct for focal drift in the z-axis often aim to hold the focal distance between the sample and the microscope objective lens fixed.